Abstract

Tools for Epigenetic Target Based Drug Discovery – Assays for Methyltranferase/Demethylase Activity and Histone Binding by NanoBRET Technology

Craig Malcolm, Strategic Collaborations Manager, Promega UK Ltd

Epigenetics is a rapidly advancing field requiring new screening tools and reagents to enable high-throughput screening groups to discover molecules which modulate key epigenetic targets. This technology snapshot will describe several new Promega assays for working with target proteins which are modulated by changes in methylation status. The presentation will include Methyltransferase-Glo™ Assay, an in vitro biochemical assay which produces a light signal from any methyltransferase reaction that uses SAM (S-Adenosyl-L-Methionine) as one of reaction substrates. Additional data will be presented describing a demethylase assay applicable to JumonjiC domain-containing histone lysine demethylases (JMJCs) which play a pivotal role in determining the epigenetic status of the genome. This simple-to-use method does not require antibodies or the use of modified substrates and is applicable to the investigation of a large number of JMJC demethylases. Finally, the presentation will discuss applications of Promega’s NanoBRET technology in the study of protein-protein interactions (PPI) related to epigenetics targets (eg. bromodomain:histone interactions) showing how the methodology can detect such interactions in a robust live-cell assay format and enable the high throughput screening for small molecule PPI inhibitors.